How to initiate norepinephrine (NE) in a patient with hypotension?

How to Initiate Norepinephrine in Hypotensive Patients

Start norepinephrine at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion, preferably through central venous access, while simultaneously ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus. 1, 2, 3

Critical Pre-Administration Requirements

Fluid Resuscitation First

• Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1, 2
• Use crystalloids (normal saline or balanced crystalloids) as first-line fluid 2
• Exception: In life-threatening hypotension (systolic BP <70 mmHg), start norepinephrine immediately as an emergency measure while continuing fluid resuscitation 2, 4, 5
• Address hypovolemia aggressively—vasoconstriction in a hypovolemic patient causes severe organ hypoperfusion despite "normal" blood pressure numbers 2

When to Start Early

Consider early norepinephrine administration (simultaneously with fluids) in patients with: 5

• Profound hypotension with diastolic BP ≤40 mmHg 5
• High diastolic shock index (heart rate/diastolic BP) ≥3 5
• Acute respiratory distress syndrome where fluid accumulation would be particularly harmful 5
• Intra-abdominal hypertension 5

Preparation and Dilution

Standard Adult Concentration

• Add 4 mg norepinephrine to 250 mL D5W to yield 16 mcg/mL concentration 2, 3
• Alternative: Add 4 mg to 1000 mL D5W for 4 mcg/mL concentration 3
• Never dilute in saline alone—use dextrose-containing solutions to prevent oxidation and loss of potency 2, 3

Starting Dose

• Initial rate: 0.5 mg/h (8-12 mcg/min or 0.1-0.5 mcg/kg/min in a 70 kg adult) 2, 3
• FDA-approved starting range: 2-3 mL/min of standard dilution (8-12 mcg base/min) 3

Administration Route

Preferred Access

• Central venous access is strongly preferred to minimize extravasation risk 1, 2, 4
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 6

Peripheral Administration (Temporary)

• If central access unavailable or delayed, peripheral IV can be used temporarily with strict monitoring 2
• Use large-bore peripheral IV in a large vein, well-advanced and securely fixed 3
• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline into the site to prevent tissue necrosis 2, 4, 3

Target Blood Pressure and Titration

Initial Target

• Target mean arterial pressure (MAP) of 65 mmHg 1, 2, 6, 4
• In previously hypertensive patients, raise BP no higher than 40 mmHg below pre-existing systolic pressure 3
• Younger normotensive patients may tolerate lower MAP targets 2

Titration Protocol

• Monitor BP and heart rate every 5-15 minutes during initial titration 2
• Titrate to achieve MAP goal AND adequate tissue perfusion markers 2, 4:
  • Lactate clearance
  • Urine output >50 mL/h 2
  • Mental status improvement
  • Capillary refill normalization
  • Warm extremities
• Increase dose by 0.5 mg/h every 4 hours as needed, up to maximum 3 mg/h 2
• Average maintenance dose: 0.5-1 mL/min (2-4 mcg base/min) of standard dilution 3

Monitoring Requirements

Continuous Monitoring

• Arterial blood pressure via arterial catheter (place as soon as practical) 1, 6
• Heart rate and cardiac rhythm 2
• Signs of excessive vasoconstriction: 2
  • Cold extremities
  • Decreased urine output
  • Rising lactate
  • Digital ischemia

Avoid Common Pitfalls

• Do not rely solely on MAP numbers—monitor tissue perfusion markers 2, 6
• Do not use dopamine as first-line agent (associated with higher mortality and arrhythmias) 1, 6
• Do not use low-dose dopamine for renal protection (no benefit, strongly discouraged) 1, 6
• Do not mix with sodium bicarbonate or alkaline solutions (causes inactivation) 2

Escalation Strategy for Refractory Hypotension

Second-Line Agents

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03 units/min 2, 6
• Alternative: Add epinephrine 0.1-0.5 mcg/kg/min 1, 6
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min 1, 6

Agents to Avoid

• Phenylephrine is NOT recommended except in specific circumstances: 1, 6
  • Norepinephrine causes serious arrhythmias
  • Cardiac output documented high with persistent low BP
  • Salvage therapy when all other agents failed

Special Considerations

Septic Shock Context

• Norepinephrine is the mandatory first-choice vasopressor (strong recommendation, moderate quality evidence) 1
• Early administration in severely hypotensive septic patients increases cardiac preload and cardiac output 7
• Benefits observed even in patients with poor cardiac contractility (LVEF ≤45%) when MAP kept <75 mmHg 7

Duration of Therapy

• Continue infusion until adequate BP and tissue perfusion maintained without therapy 3
• Reduce gradually when weaning—avoid abrupt withdrawal 3
• Treatment may be required for several days in severe cases 3